Key Function Of Nervous System Enzyme Found
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Alzheimer's disease is an illness associated with aging, and characterized by the widespread death of nerve cells within the brain. One of the principal pathological hallmarks of the disease is the presence of insoluble aggregates of a specific protein fragment, called beta-amyloid. Amyloid peptides are generated through the action of protein-cutting enzymes (proteases), including BACE1 (beta-site amyloid precursor protein-cleaving enzyme 1), which cleave the amyloid precursor protein (APP) into pieces, and thereby release beta-amyloid from the surface of nerve cells. When the gene encoding BACE1 is inactivated or when BACE1 action is inhibited pharmacologically, the production of harmful amyloid from APP is prevented and Alzheimer's disease fails to develop.
However, the researchers in Germany have now discovered that the insulating myelin sheaths of peripheral nerves fail to develop properly after inactivation of the gene encoding BACE1. In addition, the bundling of fibers of small diameter pain-sensing nerve cells into so-called Remak-bundles is abnormal. Intriguingly, the researchers found high levels of an uncleaved form of a protein, type III Neuregulin-1, in the nerve cells of BACE1 mutant mice.
Dr. Alistair Garratt and Professor Carmen Birchmeier were the first to demonstrate some years ago that nerve cells produce type III Neuregulin-1 to attract Schwann cells, the insulating glia of the peripheral nervous system, to the nerve fibers. These Schwann cells migrate along the nerve fibers and produce the myelin sheaths.
The findings of the researchers at the MDC, showing that BACE1 regulates the development of the myelin sheath, together with the discovery by Dr. Willem and Prof. Haass in Munich that BACE1 specifically cleaves Neuregulin-1, shed light on the newly characterized physiological function of BACE1: it is required to process Neuregulin-1 into a form that stimulates the Schwann cells to build up thick layers of myelin. This contrasts with the function of BACE1 in Alzheimer's disease, where its activity in cutting the protein APP is detrimental to the nervous system.
After birth, mice produce much BACE1 to trigger the insulation of nerve fibers with myelin. "BACE1 has therefore also positive functions, not only bad ones", explained Dr. Garratt. If the myelin sheath is missing, or inadequately formed, it can eventually lead to nerve dysfunction, as the researchers found in mice lacking a functional BACE1 gene. "We have thus been able to bring together the field of developmental biology with that focusing on neurodegenerative diseases," commented Dr. Garratt.
The researchers would predict that inhibition of BACE1 in the adult animal should not impact on the myelination of peripheral nerves, as Neuregulin-dependent signals are then no longer required for the maintenance of myelin sheaths. The elucidation of a physiological function of BACE1 should however allow the development of inhibitors which prevent specifically the generation of amyloid in the brain.

Therapeutics In Potential $200M
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The joint development and commercialization arrangement gives Transition $7.5 million this year and the same amount in 2007, with the possibility for up to $185 million in milestone payments.
Dublin, Ireland-based Elan and Transition will share the costs and operating profits of AZD-103, and each party's cost share and ownership interest may vary during the agreement, depending on "certain [unspecified] elections that may be made."
That's where the novelty comes in.
"Right now it's a 70/30 split," with Elan paying the bulk, said Tony Cruz, chairman and CEO of Transition. "But there comes a point where we can change that - increase our position or opt out and take a more traditional licensing agreement with a royalty stream."
Cruz said his firm has no preference at the moment, and just wants to make sure the compound "gets to the finish line as fast as possible."
Oral AZD-103 breaks down neurotoxic fibrils, allowing amyloid peptides to clear the body rather than form amyloid plaques. Transition acquired the compound through its buyout in March of Ellipsis Neurotherapeutics Inc. (of which Transition previously had held shares), also based in Toronto.
"When two amyloid betas get together and aggregate, the initial interaction is very weak," Cruz said, but then they start clumping more seriously, and the disease is difficult to stop.
AZD-103, which crosses the blood-brain barrier through an existing transporter, "prevents the interaction, and displaces existing aggregates by binding or competing at the same site," Cruz told BioWorld Today, adding that six-month studies showed no toxicity, despite giving the highest feasible toxicity dose to animals.
"We've searched 750 molecules, all in the same area, with very similar structures," and none could do what AZD-103 has done, at least so far, Cruz said.
News of the Transition deal didn't do much for Elan's shares (NYSE:ELN), which closed Wednesday at $15.54, up 2 cents.
Elan still suffers from problems with Tysabri (natalizumab), the multiple sclerosis drug partnered with Cambridge, Mass.-based Biogen Idec Inc. The firms withdrew Tysabri in February 2005, several months after launch, because of its link to cases of progressive multifocal leukoencephalopathy. This summer, the FDA allowed Tysabri back on the market, but many doctors have been wary of using it except in the sickest or refractory patients. (See BioWorld Today, June 6, 2006.)
Doing better for Elan is Prialt (ziconitide), the pain drug launched in the first quarter of 2005, which tallied full-year revenue of $6.3 million. Tokyo-based Eisai Co. Ltd. bought the European rights to Prialt early this year in a deal worth up to $100 million. (See BioWorld Today, Feb. 10, 2006.)
Eisai sells the world's leading Alzheimer's therapy, Aricept (donepezil), an acetylcholinesterase inhibitor approved by the FDA in 1996.
Two of Elan's compounds from its Alzheimer's disease immunotherapy program, partnered with Madison, N.J.-based Wyeth, are moving through the clinic. Phase II trials testing AAB-001, a humanized monoclonal antibody to A-beta, will undergo an interim analysis in the second half of this year, which also is when the interim peek is due for Phase I trials with ACC-001 (active A-beta immunotherapeutic conjugate). Elan also is moving forward with its own internal gamma and beta secretase Alzheimer's programs.
"They know this disease very well," Cruz said, conceding that Elan is "mitigating [its] risk, probably" with the Transition deal, but AZD-103 offers a different mechanism of action. "We did have multiple players at the table," he said.
Also in the Transition pipeline is a Phase II diabetes program, called Islet Neogenesis Therapy and partly partnered with Novo Nordisk AS, of Bagsvaerd, Denmark, in a potential $46 million deal. Novo has exclusive worldwide rights to research that combines an epidermal growth factor analogue with a gastrin analogue.
A separate program combines Byetta (exenatide, launched last year by Amylin Pharmaceuticals Inc., of San Diego) with gastrin to turn on the regeneration of islets in the body. Long-acting analogues of glucagon-like peptide-1 such as Byetta regulate blood glucose, but are approved only for a specific population of non-insulin-dependent diabetics.
The 70/30 structure of the Alzheimer's deal with Elan, including options for ownership change later, proves "a nice concept that I think others should use," Cruz said. "It's good for [Elan] and it's good for us."

Microscopic Brain Damage Detected In Early Alzheimer's Disease
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Researchers have developed a new computer-aided analysis technique to identify early cellular damage in Alzheimer's disease (AD). The study is featured in the October issue of Radiology.
"With increasing longevity among the population, the incidence of AD is expected to rise rapidly, creating a great burden not only for patients and their families, but also for society," said Min-Ying Su, Ph.D., author and associate professor in the Department of Radiological Sciences & the Tu and Yuen Center for Functional Onco-Imaging at the University of California at Irvine. "Our methods may enable earlier diagnosis of AD, allowing earlier intervention to slow down disease progression," she added.
As AD progresses, cell membranes in the brain may be damaged, allowing water molecules to move throughout the brain more freely. This phenomenon can disrupt neural processes and cause neuron cells to die, leading to brain atrophy. This process of cellular damage causes an increase in the "apparent diffusion coefficient," or ADC, which is a measurement used to study the distribution of water in the brain.
Thirteen elderly patients with mild cognitive impairment (MCI) were enrolled in Dr. Su's study. Patients with MCI are at high risk for developing AD. These 13 patients and 13 elderly control subjects underwent magnetic resonance imaging (MRI) of the brain and performed recall tasks. On MRI images, ADC values were measured in gray- and white-matter regions by using the computer-aided analysis program. Findings were compared between patients and healthy controls.
The computerized mapping technique allowed researchers to evaluate ADC values in large regions of the brain. In patients with MCI, researchers identified regions of brain atrophy and increased water content in white-matter areas. Additionally, high ADC values were found in the hippocampus, temporal lobe gray matter and the corpus callosum, which connects the two cerebral hemispheres. The ADC values in the hippocampus were significantly correlated with worse memory performance scores.
"The results have supported our objective to develop a computer-based analysis technique that can analyze different regions in the entire brain, to provide a comprehensive evaluation of cellular changes," Dr. Su said.
Until now, ADC values from gray matter in various lobes of the brain have not been reported, due to the difficulty of obtaining measurements in these regions. This new technology may allow researchers to learn more about how AD develops in the brain and to cultivate better treatment strategies for patients based on their individual cognitive needs.
"Patients with MCI who are very likely to progress to AD may start early treatment interventions, while patients who may remain stable with MCI can be spared from treatment and the associated side effects," added Dr. Su. "The diagnostic accuracy in identifying AD needs to be greatly improved."
AD is the most common form of dementia, affecting more than 4.5 million Americans. Patients diagnosed with AD have an average life expectancy of eight years after initial symptoms appear.

Insulin Receptor Stops Progression Of Alzheimer's Disease
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Stimulation of a receptor in the brain that controls insulin responses has been shown to halt or diminish the neurodegeneration of Alzheimer's disease, providing evidence that the disease can be treated in its early stages, according to a study by researchers at Rhode Island Hospital and Brown Medical School.
"That was the most spectacular," de la Monte says, "because everybody wants something for cognitive impairment, and that was the most improved with the PPAR delta agonist."
Researchers were not able to stop the deterioration of insulin and its receptors. However, by administering PPAR, they were able to bypass the defects in insulin signaling and preserve the cells that need insulin to thrive. PPAR molecules go directly to the nucleus of cells and tell DNA to turn on or off genes that are normally regulated by insulin, thus preventing them from dying and allowing them to communicate with each other. The major effects of the PPAR treatments were to increase brain size, preserve insulin and IGF-II receptor bearing neurons, and preserve learning and memory.
"The trigger for dementia is the loss of insulin and IGF producing cells. The cells that need those growth factors subsequently die. This study shows you can block the second phase, which is responsible for dementia. This is great news for patients since you treat early stages of disease," de la Monte says.
Another promising result for Alzheimer's patients is that these drugs could be given in the form of a pill, de la Monte says. In the study, the drugs were injected to control the amounts administered.
"One of the most exciting findings was that peripheral (intraperitoneal) injection of the PPAR agonists either partially or completely rescued the brains from neurodegeneration," the authors write.
Alzheimer's appears to be caused by parallel abnormalities – impaired insulin signaling and oxidative stress, which is regulated by the genes NOS and NOX. The PPAR agonists treatments target both problems. They preserve the cells regulated by insulin and IGF, and they decrease oxidative stress, resulting in fewer lesions in the brain.
"If the diagnosis is suspected or patients are in the early phases of AD, there's a good possibility they could get treatment that will help them. It's possible that in the moderate phase, treatment will also help, but more work needs to be done to show that," de la Monte says.
Treatment is not likely to work in the late stages of the disease, she says, because the cells have already died.

A microarray blood test for Alzheimer's disease?
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Diagnosis of Alzheimer’s disease is both art and science, relying on a thorough medical history, the identification of complicating and confounding conditions, a neurological workup, as well as a number of bioassays. Still, especially at the early stages of the disease, diagnoses (especially, diagnoses that would distinguish AD from other senile dementias with different etiologies and prognoses) are less than 100% accurate.
This is particularly tragic in light of the potential for early intervention to make the greatest difference. A highly accurate, minimally invasive bioassay for early AD would be of great value to physicians treating the disease (not to mention, to their patients and their loved ones).
Progress in this direction has been reported by Maes et al., who describe a characteristic change in genome-wide mRNA levels in the peripheral blood of AD patients:
We evaluated pathomechanisms and systemic manifestations of Alzheimer disease (AD), an aging-related dementing neurodegenerative disorder, by expression profiling. Blood mononuclear cell (BMC) transcriptomes of sporadic AD subjects and aged-matched normal elderly controls (NEC) were compared using the human NIA microarray. Relative to the NEC samples, the Alzheimer BMC exhibited a significant decline in the expression of genes concerned with cytoskeletal maintenance, cellular trafficking, cellular stress response, redox homeostasis, transcription and DNA repair. We observed decreased expression of several genes which may impact amyloid-beta production and the processing of the microtubule-associated protein tau. … BMC are highly accessible and may reflect molecular events germane to the neuropathophysiology of AD.
The particular genes affected are interesting in and of themselves; I wouldn’t have necessarily predicted that amyloid ß and tau processing phenotypes would be detectable in lymphocytes. The fact that they are suggests that the molecular defects in AD are present throughout the body, but have pathological outcomes only in the brain.
From the standpoint of diagnostics, however, the nature of the specific gene expression profile is less important than the observation of a profile per se: To the extent that this is reproducible, the blood cell mRNA profile could form the basis of a microarray-based diagnostic blood test that would provide unambiguous identification of AD (vs. other senile dementias, or other conditions that can confound diagnosis).
It remains to be seen how early in the progression of the disease this expression profile emerges, or whether its magnitude tracks the severity of the disease. If it is shown to be a leading indicator of pathology, a diagnostic tool of this kind could be invaluable in the preventive care of Alzheimer’s disease.

'Seeds' of memory loss
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Scientists injected a sticky goo from Alzheimer's victims into the brains of mice and watched it take over, provocative research that promises to help shed new light on the earliest stages of the disease.
No one knows whether this sticky protein, called beta-amyloid, actually causes Alzheimer's, but it is the chief suspect, and the new study adds to the evidence.
The German-led study found that a tiny clump of bad beta-amyloid triggers a buildup that results in Alzheimer's hallmark brain-crusting plaques -- by physically pushing nearby healthy proteins into rotten shapes.
"It's a very exciting paper," said Dr. Sam Gandy, a neuroscientist and amyloid expert at Philadelphia's Thomas Jefferson University who assessed the study on behalf of the Alzheimer's Association.
"This may give us a novel way to try and understand the way amyloid changes its shape to become toxic, become poisonous," he explained.
Moreover, there appear to be different strains of abnormal amyloid, lead researcher Mathias Jucker, a neurology professor at Germany's University of Tubingen, reported in the journal Science. If scientists can determine which version drives plaque buildup, it may point to ways to attack Alzheimer's before it gains too big a hold on the brain, he said.
"Identification of this misfolded, initiating a-beta -- that will be the big thing," Jucker said.
Alzheimer's gradually robs sufferers of their memories and ability to care for themselves, eventually killing them. There is no known cure; today's drugs only temporarily alleviate symptoms.
All brains contain beta-amyloid, although healthy cells somehow get rid of excess amounts. But in Alzheimer's patients' brains, abnormal beta-amyloid builds up into distinctive clumps, or plaques.
What makes good beta-amyloid turn bad is a mystery.
But the new study suggests that once that first little clump forms, it acts as a seed that corrupts nearby healthy amyloid, said co-author Lary Walker of Emory University's Yerkes National Primate Research Center in Atlanta.
It's similar to the way one crystal can spark others to form, a domino effect very similar to that seen in mad cow disease and other neurodegenerative diseases that are caused by abnormally shaped proteins called prions.
No one is suggesting Alzheimer's is infectious like prion diseases are, both Walker and Gandy stressed. Scientists were able to trigger Alzheimer's-like plaques in the mouse brains only because they used mice genetically engineered to be particularly vulnerable to human amyloid -- they were going to get sick anyway, but the "seeds" hastened the process.

Brain Protein May Snip at Alzheimer's
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A brain protein may curb brain plaque tied to Alzheimer's disease, possibly inspiring new treatments.
The protein is called cathepsin B (CatB). It's the subject of a study published in Neuron.
The researchers included Sarah Mueller-Steiner, PhD, and Li Gan, PhD, of the University of California, San Francisco.
In test tube experiments, they found that CatB cuts through certain amyloid-beta proteins in brain plaque linked to Alzheimer's disease.
The researchers also turned off the CatB gene in mice. After that, those mice showed higher levels of amyloid-beta proteins and brain plaque.
Then the scientists took the opposite approach. They boosted CatB levels in elderly mice that already had brain plaque. After that, the mice's brain plaque piles became smaller.
"Insufficient CatB activity might promote AD (Alzheimer's disease), while increasing CatB activity could counteract the neuropathology of this disease," the researchers write.
By "neuropathology," they mean brain abnormalities.
Gan spoke about the findings in a news release from the Gladstone Institute of Neurological Disease, which is affiliated with the University of California, San Francisco.
"We were very surprised and excited to find that CatB might be protective," Gan says.
"The number of drugs for the treatment of AD is very small. CatB's ability to remove [amyloid beta] may lead to another strategy for treating this disease," Gan adds.
Gan's team hasn't studied CatB in people yet. More research is needed before any new treatments are created.

Promising New Alzheimer's Treatment
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The new 18-month study, which will be conducted in partnership with the Trinity College Institute of Neuroscience in Dublin, Ireland, will help determine if the hypertension (high blood pressure) drug Nilvadipine could be useful in the treatment of Alzheimer's disease. In pre-clinical studies on mice, Nilvadipine was found to decrease the levels in the brain of a protein called amyloid. It is the presence of amyloid in the brain that is believed to cause the onset of Alzheimer's. The drug was also found to increase the flow of blood to the brain, which is believed to be beneficial in the treatment of the disease.The purpose of the study is to determine whether the drug will have the same effect on humans suffering from Alzheimer's as it did in the pre-clinical studies on mice. The pilot study will be a first step in trying to develop a potential treatment for Alzheimer's disease, and if successful, could change the direction of other studies of dementia. The study will be directed by Roskamp researchers Doctors Michael Mullan and Fiona Crawford, as well as a team of top neuroscience researchers in Ireland."This study is both exciting for the Roskamp Institute and its researchers, and encouraging for the millions of Alzheimer's sufferers," stated Dr. Mullan, the institute's executive director. "As scientists, we are always cautious when testing new drug therapies and are careful not to unrealistically raise expectations and hopes too high. The road to finding a cure for Alzheimer's disease is a long one, but it is our hope that the research gained through this study will put us one step closer to that ultimate goal.""I can think of no better way to commemorate World Alzheimer's Day than by announcing this exciting new clinical study," stated Chuck Albrecht, senior vice president of the Alzheimer's Association - Florida Gulf Coast Chapter, which through its nine regional offices provides support to people living with Alzheimer's disease and their caregivers, patient and family services, education, advocacy and research."We are all proud that some of the world's most cutting-edge Alzheimer's research is being done right here in Florida at the Roskamp Institute," Albrecht continued. "On behalf of the Alzheimer's Association, I would like to congratulate the Roskamp Institute on the launch of their new study, and wish them all the best in the hope of its success."While the clinical study itself will be conducted in Ireland, there are several supporting studies which will be conducted in the Tampa Bay area. To assist with its research, the Roskamp Institute is looking for volunteers who have been diagnosed with Alzheimer's disease. Participants will be asked to give a small amount of blood on three occasions over a four-week period. Though no drug will be administered during this research, this investigation will provide critical data to supplement the human clinical study being conducted in Ireland."As we prepare to observe World Alzheimer's Day, it is fitting to note that people here in Florida can play a direct role in aiding the research we are doing in Ireland," stated Dr. Fiona Crawford, the institute's deputy director. "The fight against Alzheimer's is going to take a global effort and the Roskamp Institute is honored to be playing a part."The Roskamp Institute is devoted to understanding causes of and finding cures for diseases of the mind like neuropsychiatric and neurodegenerative disorders and addictions. The Institute utilizes a broad range of scientific approaches to understanding the causes of and potential therapies for these disorders with an emphasis on Alzheimer's disease.

Alzheimer's: a century of bafflement
Ex-astronaut raises a glass to battle Alzheimer's

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Former Canadian astronaut Dr. Roberta Bondar has this image of being like everyone's squeaky clean aunt. She is fond of saying things like science is good for girls, that you should eat well and get lots of exercise. But on this sunny morning in both Toronto and Vancouver, she is on the telephone from the eastern city, touting the benefits of cabernet sauvignon wine. Once a navigator of the skies, Bondar is now an explorer of the earth.
The latest research, she says, indicates the wine can help to prevent and stall the effects of Alzheimer's disease. Who knew? Alzheimer's awareness happens to be Canada's first female astronaut's latest earth-bound mission.
It's a timely one, too. The year 2006 marks the hundredth anniversary of the identification of the degenerative brain disease by Dr. Alois Alzheimer. In a study in 1906 that broke new ground in knowledge about dementia, German doctor Alois Alz-heimer presented the case history of a 51-year-old woman, Auguste D. Alzheimer presented his findings at a conference at the University of Tuebingen in November 1906. But for the next eight decades knowledge of the disease that bore his name stayed to a large degree unchanged.

On Thursday, which is World Alzheimer's Day, she will be hosting a public forum on the disease at Vancouver's Italian Cultural Centre. It is the fourth in a series of public forums called Mission for Memories across Canada to promote awareness of the disease and to encourage people to seek treatment.
With the greying of Canada's population, the ravages of the devastating illness are sure to be more widely felt. The creeping, incurable brain disease gradually robs sufferers of their memories and ability to care for themselves. Loved ones may be forgotten. The disease is always fatal. Nancy Reagan described the late U.S. president Ronald Reagan's decline as "the long goodbye."
Health Canada forecasts almost a doubling in the number of people suffering from Alzheimer's and other dementias over the next two decades, to 772,000 in 2026 from 435,000 this year.
So does that mean we should all head out and stock up on cabernet sauvignon?
Bondar, for one, has some in her cupboard. "It is one of my favourite grapes," said the esteemed neurologist and 60-year-old native of Sault Ste. Marie, Ont. She added with a laugh, "I probably won't be putting a straw through the cork or putting it into an i.v. drip, but I find it very interesting."
What Bondar is referring to is a recent study from the Mount Sinai school of medicine in the U.S. in which wine was added to the drinking water of mice with a genetic mutation for Alzheimer's disease.
It acted as a kind of cleanser for a gooey protein called beta-amyloid, which builds up in the brains of Alzheimer's patients. The plaque is a hallmark of the disease.
The results are to be published next month. Then the clinical studies will begin. This is just one of the recent discoveries about the disease, says Bondar.
Not that she is advising Canadians to go out on a wine-drinking bender. While Alzheimer's is incurable, there is more and more evidence, she says, that it might be at least partly preventable.
There are a number of studies indicating that people with a higher educational level, which is suggestive of a higher level of cognitive function, are less likely to get Alzheimer's disease.
Also, there is a higher incidence of Alzheimer's among diabetics who have vascular disease. This suggests that treatment of disorders affecting blood vessels, such as high cholesterol and blood pressure, could be helpful in preventing Alzheimer's.

Today, though, the news about this darkest of diseases burns with a flame of hope.
Alzheimer's is being attacked on so many fronts that some researchers, while balking at talk of a cure, believe a treatment to slow or possibly stop its clinical advance is tantalisingly within reach.

Restricting Calories May Prevent And Reduce Alzheimer's Disease
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A new study directed by Mount Sinai School of Medicine extends and strengthens the research that experimental dietary regimens might halt or even reverse symptoms of Alzheimer's Disease (AD). The study entitled "Calorie Restriction Attenuates Alzheimer's Disease Type Brain Amyloidosis in Squirrel Monkeys" which has been accepted for publication and will be published in the November 2006 issue of the Journal of Alzheimer's Disease, demonstrates the potential beneficial role of calorie restriction in AD type brain neuropathology in non-human primates. Restricting caloric intake may prevent AD by triggering activity in the brain associated with longevity. "The present study strengthens the possibility that CR may exert beneficial effects on delaying the onset of AD- amyloid brain neuropathology in humans, similar to that observed in squirrel monkey and rodent models of AD," reported Mount Sinai researcher Dr. Pasinetti and his colleagues, who published their study, showing how restricting caloric intake based on a low-carbohydrate diet may prevent AD in an experimental mouse model, in the July 2006 issue of the Journal of Biological Chemistry. "This new breakthrough brings great anticipation for further human study of caloric restriction, for AD investigators and for those physicians who treat millions of people suffering with this disease" says Giulio Maria Pasinetti, M.D., Ph.D., Professor of Psychiatry and Neuroscience, Director of the Neuroinflammation Research Center at Mount Sinai School of Medicine and lead author of the study. "The findings offer a glimmer of hope that there may someday be a way to prevent and stop this devastating disease in its tracks." AD is a rapidly growing public health concern with potentially devastating effects. An estimated 4.5 million Americans have AD. Presently, there are no known cures or effective preventive strategies. While genetic factors are responsible in early-onset cases, they appear to play less of a role in late-onset-sporadic AD cases, the most common form of AD. In this new study, Dr. Pasinetti at Mount Sinai School of Medicine, in collaboration with Dr. Donald Ingram at the Laboratory of Experimental Gerontology, National Institute on Aging, NIH, maintained the Squirrel Monkeys on calorie restrictive or normal diets throughout their entire lifespan until they died of natural causes. The researchers found that a 30% calorie restriction resulted in reduced AD type amyloid neuropathology in the temporal cortex relative to control fed monkeys. The decreased AD type neuropathology correlated with increased longevity of related protein SIRT1, located in the same brain region that influences a variety of functions including aging related diseases. Collectively, the study suggests that the investigation of calorie restriction in non-human primates may be a valuable approach towards understanding the role of calorie restriction in human AD pathology. The present study strengthens the possibility that calorie restriction may exert beneficial effects in delaying the onset of AD. The findings also elucidate the important relationship between the expression of longevity genes like SIRT1 in calorie restriction dietary regimens and mechanisms associated with the prevention of AD.

Alzheimer's Disease and Red Wine
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A new study directed by Mount Sinai School of Medicine has found that moderate red wine consumption in a form of Cabernet Sauvignon may help reduce the incidence of Alzheimer's Disease (AD). The study entitled "Moderate Consumption of Cabernet Sauvignon Attenuates Б-amyloid Neuropathology in a Mouse Model of Alzheimer's Disease" is in press, and will be published in the November 2006 issue of The FASEB Journal. The breakthrough study will also be presented at the "Society for Neuroscience Meeting" held in Atlanta, Georgia, October 14-18, 2006.
"Our study is the first to report that moderate consumption of red wine in a form of Cabernet Sauvignon delivered in the drinking water for ~7 months significantly reduces AD-type Б-amyloid neuropathology, and memory deterioration in ~11-month-old transgenic mice that model Alzheimer's Disease," reported researchers Dr. Giulio Maria Pasinetti and Dr. Jun Wang at Mount Sinai. "This study supports epidemiological evidence indicating that moderate wine consumption, within the range recommended by the FDA dietary guidelines of one drink per day for women and two for men, may help reduce the relative risk for Alzheimer's Disease clinical dementia."
"This new breakthrough is another step forward in Alzheimer's research at Mount Sinai and across the globe for this growing health concern that has devastating effects," say Giulio Maria Pasinetti, M.D., Ph.D., Professor of Psychiatry and Neuroscience, Director of the Neuroinflammation Research Center at Mount Sinai School of Medicine and lead author of the study and Dr. Jun Wang, Assistant Professor of Psychiatry and co-Author of the study. "These findings give researchers and millions of families a glimpse of light at the end of the long dark tunnel for future prevention of this disease."
People with Alzheimer's Disease exhibit elevated levels of beta-amyloid peptides that cause plaque buildup in the brain, which is the main characteristic of Alzheimer's Disease. An estimated 4.5 million Americans have AD. Presently, there are no known cures or effective preventive strategies. While genetic factors are responsible in early-onset cases, they appear to play less of a role in late-onset-sporadic AD cases, the most common form of AD. However, lifestyle factors such as diet and now moderate wine consumption are receiving increasing attention for its potential preventative impact on Alzheimer's Disease.
Using mice, with AD-type Б-amyloid (AБ) neuropathology, researchers at Mount Sinai tested whether moderate consumption of the red wine Cabernet Sauvignon changes AD-type neuropathology and cognitive deterioration. The wine used was delivered in a final concentration of approximately 6% ethanol. It was found that Cabernet Sauvignon significantly reduced AD-type deterioration of spatial memory function and AБ neuropathology in mice relative to control mice that were treated with either a comparable amount of ethanol or water alone. Cabernet Sauvignon was found to exert a beneficial effect by promoting non-amyloidogenic processing of amyloid precursor protein, which ultimately prevents the generation of Alzheimer's Disease Б-amyloid neuropathology.

A Protective Mechanism Against Neuronal Death In Alzheimer's
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Researchers have uncovered a natural protective mechanism against neuronal death in Alzheimer's and similar neurodegenerative diseases. They discovered that a particular enzyme snips apart the abnormal tangles of protein called tau that are associated with cognitive decline; The enzyme, called PSA, may prove to be a promising drug target.

FINDINGS:UCLA researchers have uncovered what appears to be a natural protective mechanism against a central cause of neuronal death in Alzheimer's and similar neurodegenerative diseases. They discovered that a particular enzyme snips apart the abnormal tangles of protein called tau that are associated with cognitive decline and neurodegeneration in Alzheimer's and similar diseases.

IMPACT:The study suggests it may be possible to use drugs to enhance that mechanism and alleviate the pathology of Alzheimer's and similar diseases.

Early Memory Lapses Could Warn of Alzheimer's
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Older adults who complained of recurrent memory loss had brain changes that mirrored those of very early Alzheimer's -- even when standard cognitive tests came up normal, a new study reports.
Based on these findings, "cognitive complaints should be taken very seriously -- these are not necessarily just the 'worried-well,'" said researcher Andrew Saykin, a professor of psychiatry and radiology at Dartmouth Medical School, in Lebanon, N.H. "Those with significant cognitive complaints and concerns should talk with their physicians and get a thorough evaluation."
The findings were published in the September issue of Neurology.

The findings echo those of another study of older adults, published in Neurology in June. In that research, a team at Rush University, Chicago, found that episodic memory failure corresponded with signs of early, undiagnosed Alzheimer's in brain tissues examined post-mortem.
Although the findings do point to memory lapses as perhaps indicative of very early Alzheimer's disease, "I wouldn't necessarily look at it as something to be extremely concerned about," Dr. Sam Gandy, chairman of the Alzheimer's Association's Medical and Scientific Council told HealthDay at the time. He said the results of the Rush study suggest potential new avenues for early diagnosis and treatment.
Cole noted that occasional "cognitive complaints" -- forgetting keys, or failing to remember PIN codes at the bank -- do occur, of course, and can be a cause for worry. But age-related forgetfulness can be caused by a variety of conditions, including non-Alzheimer's-related vascular disease, he pointed out.
"This study took a comprehensive look and defined a subset of people who have essentially episodic problems yet do well on tests," Cole said. In other words, their forgetfulness occurred frequently and was noted by loved ones, yet the usual tests showed no obvious problem.
Here, however, "the researchers verified the gray matter changes that indicate disease prior to minimal cognitive impairment," Cole said. "They're clicking back the ability to detect incipient Alzheimer's disease with some better confidence that it's truly Alzheimer's disease."
That could lead to the use of neuro-protective agents five, 10 or 20 years before people meet the diagnostic criteria for Alzheimer's, the experts said, to help delay symptoms.

Know the right herb for the right problem
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HUNTINGTON -- Madison Reed, owner of the New Earth Resource Co. at 826 10th St., said that there are plenty of people who'd like to try herbal supplements, but they simply don't know where to start.
He suggested a few of his favorite or most popular herbs in from his Huntington shop.

TURMERIC ROOT: "This has properties that can reduce inflammation anywhere in the body as well as, if not better than, Prednisone or other inflammation-reducing drugs. Plus, in South Korean medical studies, curcumin, the active ingredient in turmeric root, has been shown to reduce beta amyloid plaque in the brains of Alzheimer's patients and help it cross the blood-brain barrier."
CINNAMON BARK: "If it's really good cinnamon bark. It tastes delicious, so you can use the powdered cinnamon bark in teas and it helps to balance and regulate insulin. So it's very good for people with diabetes."
SCULLCAP: "This will, without interfering with motor coordination, put you in a serene state, where you're not nervous, and you just feel wonderful. But it's not a drug effect, it's not addictive. A lot of times, I mix it with a little spearmint leaf, to give it a bit more taste."
UVA URSI AND USNEA LICHEN: "What's wonderful about this is that someone can drink this and very, very quickly wipe out a urinary tract infection. I know that it works better than cranberry. The old cranberry recommendation for UTIs isn't as effective. Typically, people make the mistake of getting the cranberry with sugar or some sort of corn sweetener, and that can just irritate their urinary tract infections."
More information about these herbs and many others is available by calling Reed at (304) 697-4421.

A Second Dimension To Alzheimer's Disease
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The researchers found that two genes mutated in familial Alzheimer's disease known as presenilins may control the balance of calcium within cells by acting as a calcium channel. Calcium is an important signaling molecule, with effects on the nervous system that include functions relevant to learning and memory, the researchers said. The research team also discovered that the mutant forms of presenilin--which have been linked to about 40 percent of familial Alzheimer's disease cases--lose the ability to serve this function.
Presenilins are primarily known for their role as an enzyme that cleaves amyloid precursor protein (APP) to form amyloid ß-peptide, the principal constituent of the plaques that riddle the brains of Alzheimer's patients.
Alzheimer's disease affects nearly 2% of the population in industrialized countries. Most cases of the disease are of unexplained origin and are characterized by late onset in people over the age of 60. A small fraction of cases are characterized by an earlier onset and genetic inheritance.
Earlier studies had linked mutations in the presenilin gene to abnormal calcium signaling and suggested that calcium might have some relevance to Alzhiemer's disease. However, the mechanistic basis for presenilin's apparent effects on calcium remained unclear, leaving a question as to whether the proteins played a direct role.
The researchers now report from studies in mice that presenilins can form ion channels. The effects of presenilin could account for about 80% of the calcium leaked from a membrane bound cellular compartment called the endoplasmic reticulum, they found.
Cells with the mutant presenilin become "overloaded" with calcium, Bezprozvanny explained, which heightens the strength of the calcium signal. Moreover, the heightened calcium signal was reversed in mutant cells in which the scientists restored normal presenilin. They further showed presenilin's role in calcium signaling to be independent of its role in the production of amyloid ß.
The findings suggest that drugs that restore normal calcium levels might be useful for treating Alzheimer's disease, Bezprozvanny said. Indeed, he added, a drug called memantine, which is already in use against Alzheimer's, acts on receptors that are a component of the calcium pathway.
The development of Alzheimer's drugs has almost exclusively focused on amyloid plaques, he said. The current findings begin to suggest the possibility that a combination therapy targeting both amyloid and calcium signaling might be a "best case scenario," Bezprozvanny speculated.
Aberrant calcium signaling might also be a common link among multiple neurodegenerative diseases, he added. For example, he noted that his group earlier found evidence for a direct effect of abnormal calcium signaling in Huntington's disease.

Caffeine reduces Alzheimer's risk
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If you think that your daily cups of coffee only provide you with alertness after you wake up or during the day, think again. Long-term intake of caffeine, the major constituent in coffee and tea, has been shown to reduce the risk of Alzheimer’s in mice that develop the disease. In a study just published on-line in the journal Neuroscience, researchers at the Byrd Alzheimer’s Institute in Tampa, Florida, are reporting that caffeine intake equivalent to five cups of coffee a day in humans, protects Alzheimer’s mice against otherwise certain memory impairment and reduces Alzheimer’s pathology in their brains.
An earlier study in humans hinted that caffeine was protective against Alzheimer’s disease by showing that Alzheimer’s patients consumed markedly less caffeine during the 20 years preceding disease diagnosis compared with age-matched individuals without Alzheimer’s disease.
“We wanted to test the ability of dietary caffeine intake to protect against Alzheimer’s disease in a highly controlled study in Alzheimer’s mice where the only variable that was different between groups was whether caffeine was in their drinking water or not,” says Dr. Gary Arendash, Ph.D, lead researcher in the study. “We were surprised to find that Alzheimer’s mice given caffeine in their drinking water throughout adult life performed much better than Alzheimer’s mice not given caffeine and very similar to normal mice without the disease,” adds Arendash.

Not only was the memory of Alzheimer’s mice protected by the human equivalent of five cups of coffee per day (500 mg/day), but levels of an abnormal brain protein that most researchers believe causes the disease were reduced. This abnormal protein, called beta-amyloid, is formed by the actions of two enzymes on a much larger protein called APP, which extends through the cell membrane of brain cells. The two enzymes (BACE and PS1) cut APP in specific places, resulting in beta-amyloid formation. Once formed, beta-amyloid molecules aggregate into “plaques” within the brain, causing death and dysfunction of cells, especially in brain areas important for learning and memory. The researchers found that caffeine reduces the level of both BACE and PS1 enzymes, thus resulting in much less of the dangerous beta-amyloid protein.

Millions Of People Worldwide Suffer From Alzheimer's
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A hundred years ago, the psychiatrist and brain researcher described the first patient with a severe dementia accompanied by the massive loss of nerve cells (neurons). At that time, the disease later named after him was still rare. Alzheimer saw only two cases in his research career, as Dr. Christian Haass, Professor at the Ludwig Maximilian University Munich, Germany, said during the International Conference on Neurodegenerative Diseases held in the Max Delbrück Communications Center (MDC.C) in Berlin. Today, according to Dr. Haass, alone in Germany approximately 1.2 million people suffer from Alzheimer's disease. In the European Union, there are around 5 million people with dementia, of whom 60 - 70 percent are Alzheimer's patients. Around 4.5 million Alzheimer's patients live in the United States. With people's life expectancy rising, scientists fear that the number of dementia and Alzheimer's patients will double in the next 25 years if the disease cannot be successfully treated or prevented. In 1985, scientists were able to identify the insoluble deposits in the brain as amyloid-beta plaques. In recent years, scientists have gained increasing insight into the molecular mechanisms of Alzheimer's disease which they hope will provide attack points for a targeted, causative treatment of this presently incurable disease. The severe degenerative disorder of the brain in which people slowly lose their memory, their spatial orientation, their language, and the control over their body functions brings great suffering to Alzheimer's victims and their families, who often care for the patients for years. The cost of providing care for Alzheimer's patients is spiraling to billions of euros and dollars for the healthcare systems.

Untangling A Pathology Of Alzheimer's
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George Jackson, Daniel Geschwind, and their colleagues described their findings in the journal Neuron, published by Cell Press. Basically, in studies with mice, flies, and brain tissue from human patients, they discovered that the enzyme puromycin-sensitive aminopeptidase (PSA) snips apart the abnormal tangles of protein called tau that are associated with cognitive decline and neurodegeneration in Alzheimer's and similar "tauopathy" diseases.
Significantly, they found higher levels of PSA gene expression in the cerebellum than in the cortex of patients with such diseases. The former region is known to be more resistant to neurodegeneration in such diseases than the latter. Tau causes neurodegeneration when a mutant form of the protein forms "neurofibrillary tangles" in brain cells, ultimately killing them.
In their experiments, Jackson, Geschwind, and their colleagues first used DNA microarrays--so-called "gene chips"--to find genes that were more activated in certain brain regions than others, in mice engineered to have a mutant form of human tau that causes neurodegeneration. Such microarrays enable researchers to determine the activity of thousands of genes at once. The gene for PSA was among those they identified as more active in the resistant cerebellum.
In studies with the fruit fly Drosophila, they found that higher activity of the PSA gene--and loss of its function--enhanced neurodegeneration. And in test tube studies, they found that PSA does directly act on tau to snip it apart for degradation by the cell.
They next compared levels of PSA gene expression in samples of brain tissue from the cortex and cerebellum of both normal humans and those with fibrillary tangle disorders. In both types of samples, they found a 5-fold elevation of PSA in the cerebellum as compared to the cortex.
The researchers concluded that their work not only reveals a significant protective factor in fibrillary tangle disorders, but points the way for further searches of other such factors. They wrote that "This work provides a clear proof of principle for validation of genetic screens using model systems and allows us to more firmly establish a functional role for one of the identified genes, Psa. Although Psa was known to be highly brain enriched, to our knowledge, its role vis-a-vis tau degradation or modification of tau-induced neurodegeneration has not been characterized previously.

Critical Evolution Of Cells That Lead To Alzheimer's
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A buildup of amyloid beta proteins in the brain could cause good proteins to go bad, resulting in the formation of rod-like aggregates within neurons that leads to Alzheimer's disease, according to research by a Colorado State University biochemistry professor. The discovery provides new information on possible causes of Alzheimer's disease and a mechanism for its progression, and it deeDennis Selkoe, Vincent and Stella Coates Professor of Neurologic Diseases in the Department of Neurology at Harvard Medical School, has just begun a partnership with Bamburg.

“He does beautiful work,” Selkoe said. “I like what he's found in terms of the amyloid beta protein causing buildup of the cofilin rods. It is a very nice approach and very careful work.” The Colorado State discovery means scientists can begin to look at how to prevent the rods from forming. They still don't know whether the existence of rods leads to an increase in production of amyloid beta proteins, causing the cycle to continue, Bamburg said. “If rod formation generates more amyloid beta and this leads to more rod formation, we can begin to look at mechanisms to prevent rods from accumulating and perhaps even ways to eliminate rods that have formed,” Bamburg said. “Everything seems to be there for the production and processing of amyloid beta. Is it building up? Is it assembling into something more toxic that could lead to more A-beta? Is it the structure or the amount that's important? These are all questions that drive our current research but which haven't been fully answered,” he said. Individual cells have the power to migrate by assembling filaments of actin- one of the major proteins in muscle. Those filaments push the membrane forward like stretching a balloon. Actin depolymerizing factor (ADF) keeps the subunits of actin treadmilling (adding onto one end and coming off the other end), a process that is energy dependent and which can do work. Under stress, as energy declines, the sequestering of ADF into actin-containing rods lowers the actin filament treadmilling and conserves the cells chemical energy stores for other uses. Prolonged energy depletion leads to rods that become irreversible, leading to the loss of synaptic connections.pens scientists' understanding of the neurological disease, which has no cure.

Testing for Alzheimer's
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Amorfix has reached a technical milestone in the development of a blood test for Alzheimer'sCanadian biotech firm Amorfix has demonstrated that it's Epitope Protection technology is able to detect aggregated beta-amyloid, a potential biomarker for Alzheimer's disease. With current estimates suggesting that almost half of Alzheimer's sufferers across the seven major pharmaceutical markets are undiagnosed, a simple diagnostic tool monitoring a robust biological marker is in great demand.'Content Current diagnosis of Alzheimer's disease is conducted by specialists using a psychological examination, and then later verified by post-mortem analysis. While this method is accurate - up to 90% accurate when confirmed by post-mortem - the diagnosis rate is poor because many sufferers are not seen by specialist clinicians.Datamonitor estimates that there were five million Alzheimer's sufferers in the seven major pharmaceutical markets in 2005, however, only 2.8 million were diagnosed. Alzheimer's disease is associated with an accumulation of toxic aggregated beta-amyloid in the brain. Beta-amyloid is present in the blood of normal individuals, however, significant levels of the toxic aggregated beta-amyloid is believed to be present only in the circulation of Alzheimer's patients.Blood levels of aggregated beta-amyloid could be the most accurate convenient biomarker for early Alzheimer's disease detection. Early detection would represent a significant step towards effective treatments. Not only would early intervention help slow the progression of the disease, but also, such an alternative clinical trial endpoint would aid drug development. Having now made significant progress with its EP technology, Amorfix says that it is in a position to finish its development and validate a blood test for Alzheimer's disease.This news comes on the back of a successful few months for the Canadian-based theranostics company. In Aug

New Insights into the Cause of Alzheimer's Disease
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Scientists are gaining ever more insight into the causative mechanisms involved in Alzheimer's disease. Thus, they can identify possible attack points for a targeted, causative treatment of this severe brain disorder which affects millions of people worldwide, as reported at the international conference "Neurodegenerative Diseases: Molecular Mechanisms in a Functional Genomics Framework" in the Max Delbrück Communications Center (MDC.C) in Berlin-Buch (Germany). Alzheimer's, like Huntington's disease and Parkinson's disease, belongs to the group of neurodegenerative diseases caused by misfolded proteins.
"Alzheimer's is a disease of old age," Dr. Christian Haass, Professor at the Ludwig Maximilian University Munich said at the Berlin conference. In 1992, he succeeded in showing that the insoluble protein fragments that are deposited in the brains of Alzheimer's patients, the so-called amyloid beta, are continually formed in the brain throughout life and are part of the normal aging process. The scientist is convinced that all people, if they lived long enough, would fall ill with this severe degenerative disorder of the brain. Amyloid beta develops when the so-called amyloid precursor protein (APP) is broken into fragments. It quickly became clear that Amyloid beta is generated by proteolytic processing involving two types of proteases, beta-, and gamma-secretase. "Inhibiting the activity of these two enzymes should slow down nerve cell degeneration," Dr. Haass said in Berlin. These enzymes could, therefore, be potential drug targets. Yet Alzheimer's disease still baffles scientists: while they have a good understanding of how protein fragments develop, they cannot explain how these fragments prove to be toxic to nerve cells. Dr. Roberto Cappai, Professor at the University of Melbourne, Victoria, Australia, reported in Berlin that copper ions influence the formation of harmful protein deposits. The higher the level of copper in the brain, the less amyloid beta (which is neurotoxic) is formed. Scientists have been able to show that the level of copper in Alzheimer's patients is very low. Around 200 genome researchers and clinicians from Europe, Japan, Canada, and the US attended the four-day conference in Berlin, which ended on Saturday, September 9th. The conference focused on the investigation of the causes of neurodegenerative diseases with the aid of systems biology, which seeks to piece together single aspects of research that have, until now, been analyzed separately - (e.g., proteins, protein interactions, signal pathways, and cells) in order to obtain an overall picture. It was the first conference of its kind organized by the Max Delbrück Center for Molecular Medicine (MDC) Berlin Buch together with the Charité -University Medical School Berlin and the University of Bonn under the umbrella of the National Genome Research Network (NGFN).

Growth Factors In Memory Formation
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A type of protein crucial for the growth of brain cells during development appears to be equally important for the formation of long-term memories, according to researchers at UC Irvine. The findings could lead to a better understanding of, and treatments for, cognitive decline associated with normal aging and diseases such as Alzheimer's. The findings appear in the early online edition of the Proceedings of the National Academy of Sciences. "This study presents strong evidence that a molecular process fundamental during development is retained in the adult and recycled in the service of memory formation," said Thomas J. Carew, Donald Bren Professor and chair of UCI's Department of Neurobiology and Behavior. "It is a striking example of how molecular rules employed in building a brain are often reused for different purposes throughout a lifetime." The researchers have shown that proteins known as growth factors are as essential for the induction of long-term memory as they are for the development of the central nervous system. These growth factors, such as brain derived neurotrophic factor (BDNF), bind onto the brain cell through a specific type of receptor known as TrkB, much the same way a key fits into a lock. As an experimental strategy to determine the importance of BDNF-like growth factors in forming memories, the researchers used a "molecular trick" to keep the proteins from binding with the appropriate TrkB receptors.

"We would never have expected that the secretion of these growth factors in response to serotonin would be critical for long-term memory formation in this system," Carew said. "But it is apparent that without them, this process cannot happen." According to Carew, these findings could open possible avenues for treatments relating to memory loss. "This gives us some strong clues as to what we should be looking into for therapeutic interventions," he said. "If we know that growth factors are important for long-term memory, then we can look at possible remedial roles they might play in diseases such as Alzheimer's and dementia."

Mind-robbing Alzheimer’s disease curable
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An ingredient in green tea that researchers think might fight cancer may also protect the brain from the memory-destroying Alzheimer’s disease. Scientists injected mice with an antioxidant from green tea called epigallocatechin-3-gallate (EGCG) and said it decreased production of beta-amyloid, a protein that forms the plaques that clog the brains of Alzheimer’s victims. Several months of injections reduced plaque formation by as much as 54 percent, researchers from the University of South Florida wrote in the Journal of Neuroscience. The mice had been genetically programmed to develop an Alzheimer’s-like disease. Alzheimer’s is a progressive disorder that causes memory loss and afflicts an estimated 4.5 million people in the United States and millions more globally. Drinking ordinary green tea may not lead to the same plaque reduction seen in the study because other ingredients in the beverage appear to block EGCG’s benefits, said Dr. Jun Tan, the study’s senior author and director of the neuroimmunology laboratory at the Silver Child Development Center in the University of South Florida’s psychiatry department. Supplement pills containing EGCG might help, he said. Scientists are also trying to develop a tea with a high concentration of EGCG that could offer health benefits. Other studies have shown EGCG may prevent certain cancers and could block the spread of the HIV virus that causes AIDS. Humans would probably need 1,500 to 1,600 milligrams per day of EGCG to get the amount that helped mice in the Alzheimer’s study, Tan said. Researchers have tested the safety of those doses in people and found no major side effects, he said. The next step for researchers is to test an oral form of EGCG in mice and see if it protects the animals’ memory, he said. “If those studies show clear cognitive benefits, we believe (human) trials of EGCG to treat Alzheimer’s disease would be warranted,” Tan said. The study was funded by the University of South Florida College of Medicine Faculty Start-Up Funds, the Johnnie B. Byrd Sr. Alzheimer’s Center & Research Institute, the National Institute of Neurological Disorders and Stroke and the Alzheimer’s Association.

Good news for senior social butterflies and old people who are sexually active. A study has shown that old people who frequently go to parties, relate with friends and have sex are less prone to developing Alzheimer’s disease, a form of dementia that afflicts the aged. Ma. Socorro Martinez, head of the Memory Center of the St. Luke’s Medical Center, said the study done in Sweden showed that socialization reduced the risk of Alzheimer’s disease by 30 percent. “Those who don’t have a spouse tend to have Alzheimer’s disease because they have nobody to talk with,” Martinez said in a health forum.

Anticipation Plays A Powerful Role In Human Memory
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Psychologists have long known that memories of disturbing emotional events - such as an act of violence or the unexpected death of a loved one - are more vivid and deeply imprinted in the brain than mundane recollections of everyday matters.
Probing deeper into how such memories form, researchers at the University of Wisconsin-Madison have found that the mere anticipation of a fearful situation can fire up two memory-forming regions of the brain - even before the event has occurred.
That means the simple act of anticipation may play a surprisingly important role in how fresh the memory of a tough experience remains.
The findings of the brain-imaging study, which appear in the current issue of the Proceedings of the National Academy of Sciences, have important implications for the treatment of psychological conditions such as post-traumatic stress disorder (PTSD) and social anxiety, which are often characterized by flashbacks and intrusive memories of upsetting events.
"The main motivation for this study was a clinical one, in terms of understanding and applying knowledge about memory so that we can better inform the treatment of disorders that have a large memory component, like PTSD," says lead author Kristen Mackiewicz, a graduate student at the University of Colorado who worked on the anticipation study while a student at UW-Madison.
The researchers studied the brain activity of 36 healthy volunteers using a technique known as functional magnetic resonance imaging, which produces high-contrast images of human tissue. They began by showing the volunteers two kinds of signals. One was neutral, but the other indicated that some type of gruesome picture was soon to follow, such as explicit photos of bloody, mutilated bodies. Thirty minutes after the researchers had shown dozens of violent images, they quizzed study participants on how well they remembered the pictures they had just seen.
"We found that the more activated the amygdala and hippocampus had been during the anticipation [of the pictures], the more likely it was that a person would remember more of them right away," says Nitschke.

India Drug Gives Alzheimer's Hope
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Scientists in the UK and India are examining the ancient Indian ayurvedic medicine for possible use in drugs to treat Alzheimer's disease.
Researchers say ayurveda works in the same way as conventional drugs for boosting mental agility in the disease. They found that the plants used in ayurveda acted to improve memory and concentration in Alzheimer's sufferers.
Alzheimer's disease is a progressive, degenerative and irreversible brain disorder. There is no known cure. The disease causes intellectual impairment, disorientation and eventually death.
Researchers from King's College, London and Jadavpur University in the eastern Indian city of Calcutta, studied five plants commonly used in ayurvedic medicine.
They found that the plants acted to prevent the breakdown of neurotransmitters, improving memory and concentration in people with Alzheimer's disease - the most common form of dementia. The scientists are now trying to identify the chemical compounds responsible so they can be used to develop more effective drugs.
Alternative medication
Ayurveda is a 5,000-year-old Indian tradition of herbal and "alternative" medication. Ayurvedic medicine uses herbs and spices like basil, turmeric, garlic, ginger and aloe vera, as well as yoga exercises, to treat physical and psychological problems. The causes of Alzheimer's disease are not yet fully understood. There are some very rare inherited cases caused by genetic mutations, but these account for around 1% of people with Alzheimer's. Various types of therapy are used to try to stimulate Alzheimer's patients. These include: psychological methods, art therapy, music therapy, playing with toys. Some health professionals try to encourage patients to reminisce about past memories as a way to reduce depression without the use of drugs. A variety of drug treatments have been shown to benefit patients. None are a cure, but they can temporarily relieve some of the symptoms in some patients.

Cholinesterase inhibitors to people with mild to moderate Alzheimer's disease
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Since 2001, the National Institute for Health and Clinical Excellence (NICE) has recommended that cholinesterase inhibitors should be available to people with mild to moderate Alzheimer's disease, writes consultant psychiatrist, Anthony Pelosi and colleagues. This was based on evidence that these drugs slowed cognitive (mental) decline, but NICE stressed that further research was required and it planned to revisit its recommendations after several years. The guidelines were welcomed by patient and carer organisations, and a large number of specialist memory clinics were set up for the prescription and monitoring of these medicines, sometimes with funding from the drug manufacturers. But widespread clinics have distorted clinical priorities, argue the authors. They have recruited full multidisciplinary teams while there is a shortage of mental health professionals throughout the United Kingdom, and they do not offer care in the community to their patients as they decline. Patients then have to be referred to ordinary old age psychiatry teams, which have to arrange proper long-term management plans. Further research is now available and shows quite consistently that these medicines have modest beneficial effects compared with placebo. As a result, NICE recommended that the NHS should no longer prescribe cholinesterase inhibitors because they do not provide value for money. But after hostile reactions from clinicians, patients and carers, with support from the lay media, NICE now proposes restricting use to moderate Alzheimer's disease. But doctors are concerned that it will be extremely difficult (perhaps impossible) to wait for a diagnosed patient to deteriorate before starting treatment. NICE has been unfairly accused of ageism and stigmatisation of people with dementia, and it has been claimed that adoption of the revised guidelines would be devastating for patients and carers. But the tragedy is not the proposed restrictions, but the fact that the only currently licensed medicines for a cruel illness have turned out to be of marginal benefit, write the authors. Whatever the final outcome of NICE's deliberations, the human and financial resources that have become tied up in clinics organised around prescription of cholinesterase inhibitors must be diverted to old age psychiatry teams and their social care counterparts, they say. These medicines should no longer be allowed to have such influence on services for patients with Alzheimer's disease and their families.

Spectrometry Identifies Biomarkers For Dementia
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Researchers seeking new biomarkers for neurodegenerative diseases have assembled a panel of proteins that can differentiate between normal people and sufferers of Alzheimer’s disease, Parkinson’s disease, or dementia with Lewy bodies (DLB) with 95% accuracy. Investigators at the University of Washington (Seattle, USA) used the sophisticated stable isotope iTRAQ (isobaric tagging for relative and absolute protein quantification) system in conjunction with multidimensional chromatography, followed by tandem mass spectrometry (MS/MS), to simultaneously measure relative changes in the protein composition of cerebrospinal fluid (CSF) obtained from patients with Alzheimer’s disease, Parkinson’s disease, and DLB compared to healthy controls. They reported in the August 2006 issue of the Journal of Alzheimer's Disease that after analyzing more than 1,500 CSF proteins they had identified eight unique protein markers that were capable of distinguishing Alzheimer’s disease, Parkinson’s disease, and DLB patients from each other as well as from controls with high sensitivity at 95% specificity. “We are getting very close to being able to use these biomarkers for the clinical diagnosis of Alzheimer’s and Parkinson’s disease, and dementia with Lewy bodies,” said senior author, Dr. Jing Zhang, associate professor of pathology at the University of Washington. “This is a major improvement on other biomarker detection techniques.”

Alzheimer's Test
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A novel imaging agent has the potential to diagnose Alzheimer's disease in living patients by binding to the telltale beta-amyloid deposits in the brains of those who suffer from it. Pittsburgh Compound-B, or PIB, is the contrast agent used in conjunction with PET scans. This non-invasive technique can give researchers information never before available about how and where the disease progresses in the brain, as well as the efficacy of treatment.
WHAT THEY'VE FOUND: The pattern of PIB retention in the brain suggests amyloid plaques formed by Alzheimer's appearing first in the frontal cortex areas, then progressing to the parietal and temporal cortex before ravaging the occipital and sensory-motor cortex. This may explain why memory and judgment are often the brain functions first affected with the onset of the disease.
SYMPTOMS: Alzheimer's is a slow-moving disease, and in its earliest stages may merely appear to be mild forgetfulness and confused with age-related memory change. There may be problems remembering recent events or activities, or the names of familiar people or objects. As the disease progresses, the forgetfulness becomes more severe, interfering with daily activities, such as brushing one's teeth. There are problems speaking, understanding, reading or writing, and eventually the brain damage becomes so severe the patient requires 24-hour care.
FACTOID: As many as 4.5 million Americans suffer from Alzheimer's disease. While only about 5 percent of men and women ages 65 to 74 have the disease, nearly half of those 85 or older may have it.

Vegetable And Fruit Juice And Alzheimer's Risk
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If you drink fruit and/or vegetable juice at least three times a week you could be reducing your chances of developing Alzheimer's disease (AD) by 76%, say scientists in a new study. Even if you have a fruit and/or vegetable juice just twice a week your risk goes down 16%.You can read about this study in the September issue of the American Journal of Medicine.The scientists monitored nearly 1836 Japanese Americans in King County, Washington, for a decade and found that those whose consumption of fruit and/or vegetable juice was three times a week or more had a 76% lower chance of developing AD when compared to people who did so just once a week or less.Dietary consumption of fruit and vegetable juices was determined from self-administered questionnaires developed for Asian populations. Cognitive function was assessed by trained interviewers using a standardized test, with clinical follow-up resulting in clinical diagnoses for those patients showing impairment.Several studies have suggested that polyphenols might disrupt some of the processes that lead to the accumulation of beta-amyloid peptide in the brain, and thus delay the onset of AD. Previous studies have indicated that the accumulation of beta-amyloid peptide in the brain is linked to a higher incidence of AD. Polyphenols are strong anti-oxidants which are available in many foods, especially fruits and vegetables.This is the first study to look at juices rich in polyphenols as a preventative measure for AD.Team member, Qi Dai, MD, PhD, wrote, “We found that frequent drinking of fruit and vegetable juices was associated with a substantially decreased risk of Alzheimer's disease. This inverse association was stronger after adjustments for potential confounding factors, and the association was evident in all strata of selected variables. These findings are new and suggest that fruit and vegetable juices may play an important role in delaying the onset of Alzheimer's disease”.

Spectrometry Identifies Biomarkers For Dementia...